Redistribution of vitamin A after iron supplementation in Indonesian infants

BACKGROUND: Deficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. OBJECTIVE: This study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements. DESIGN: In a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. RESULTS: Iron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the non-supplemented infants. In contrast, the modified relative dose response of the iron-supplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but beta-carotene supplementation did not significantly improve vitamin A status. CONCLUSIONS: In this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status.     

Combined iron and zinc supplementation in infants improved iron and zinc status, but interactions reduced efficacy in a multicountry trial in southeast Asia

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n=2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P<0.01) and zinc deficiency by 10% (P<0.05) but was less effective (P<0.05) than supplementation with either iron (28% reduction in anemia) or zinc alone (18% reduction in zinc deficiency). Iron reduced the effect of zinc supplementation (interaction P<0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-2.5 g/L, P<0.001), independent of iron supplementation (Pinteraction=0.25). The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls (effect size 12.0 vs. 6.8 g/L, respectively). In infants not receiving iron, VAC administration tended to be associated with lower (3.2%, P=0.07) hemoglobin concentrations. Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies. Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status. Furthermore, VAC administration in the absence of iron supplementation may increase the incidence of anemia.     

Subtyping Stereotypic Behavior in Children: The Association Between Stereotypic Behavior, Mood, and Heart Rate

The Stereotypic behavior of children (N = 26) while in a playroom session with their parent was studied. The sample included children with a pervasive developmental disorder, an attention-deficit/hyperactivity disorder, a developmental expressive language disorder, or a developmental receptive language disorder and normally developing children. Stereotypic behaviors associated with distress, elation, and composure were compared on mean duration and form of the stereotypies and heart rate changes around the onset of the stereotypies. Results showed that stereotypies associated with different moods differed in all variables studied. Results confirm that a valid classification scheme for Stereotypic behaviors is needed as they indicate different functions of individual stereotypies.     

Strategies to prevent iron deficiency and improve reproductive health

Anemia and iron deficiency affect billions of people worldwide, especially women of reproductive age, pregnant women, and young children. Many countries have iron and folic acid supplementation programs for pregnant women. However, the impact of these programs is uncertain. Multiple-micronutrient supplementation during pregnancy has been advocated; however, it is unclear whether this has additional advantages. Overall, programs have shown only modest impact on increasing birth weight. This review discusses the present state of knowledge on interventions to improve iron status during pregnancy and reproductive health, and investigates other possibilities such as supplementation prior to conception to improve maternal and child health.     

Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia

Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies.     

Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants

Many indicators of micronutrient status change during infection because of the acute phase response. In this study, relationships between the acute phase response, assessed by measuring concentrations of C-reactive protein (CRP), alpha(1)-antichymotrypsin (ACT) and alpha(1)-acid glycoprotein (AGP), and indicators of micronutrient status were analyzed in 418 infants who completed a 6-mo randomized, double-blind, placebo-controlled, supplementation trial with iron, zinc and/or beta-carotene. The acute phase response, defined by raised CRP (plasma concentration >10 mg/L), raised AGP (>1.2 g/L), or both raised CRP and AGP, significantly affected indicators of iron, vitamin A and zinc status, independently of the effects of supplementation. Plasma ferritin concentrations were higher by 15.7 (raised AGP) to 21.2 (raised CRP and AGP) micro g/L in infants with elevated acute phase proteins compared with infants without acute phase response (P < 0.001). In contrast, plasma concentrations of retinol were lower by 0.07 (P < 0.05, raised AGP) to 0.12 (P < 0.01, raised CRP) micro mol/L, and of zinc lower by 1.49 (P < 0.01, raised AGP) to 1.89 (P < 0.05, raised CRP and AGP) micro mol/L. Hemoglobin concentrations and the modified relative dose response were not affected. Consequently, the prevalence of iron deficiency anemia was underestimated in infants with raised acute phase proteins by >15%, whereas the prevalence of vitamin A deficiency was overestimated by >16% compared with infants without acute phase response. Hence, using indicators of micronutrient status without considering the effects of the acute phase response results in a distorted estimate of micronutrient deficiencies, whose extent depends on the prevalence of infection in the population.     

Assessment of the effect of ribavirin on myeloid and plasmacytoid dendritic cells during interferon-based therapy of chronic hepatitis B patients

The combination of ribavirin and peginterferon is the current standard of anti-viral treatment for chronic HCV patients. However, little is known on the mode of action of ribavirin in the anti-viral treatment of HCV patients. To investigate the immunomodulatory mechanism of ribavirin, we studied peginterferon alone versus peginterferon and ribavirin in chronic HBV patients. The addition of ribavirin did not affect the number of myeloid dendritic cells (mDC) or plasmacytoid dendritic cells (pDC), nor did it enhance T-helper-1 cell activity or T-cell proliferation. In contrast, it increased upregulation of activation markers on mDC and pDC, which was sustained throughout treatment. However, the addition of ribavirin had no effect on IFNα production by pDC. Our findings demonstrate that, although ribavirin does not lead to a viral load decline, in vivo treatment with ribavirin affects the activation of pDC and mDC in chronic HBV patients.